tbuckley/cabot-search huggingface dataset:
Multilineage commitment of Sca-1<sup>+</sup> cells in reshaping vein grafts
Authors: Zhichao Ni, Lingxia Lyu, Hui Gong, Luping Du, Zuoshi Wen, Hua Jiang, Hao Yang, Yanhua Hu, Bohuan Zhang, Qingbo Xu, Xiaogang Guo, Ting Chen
Journal: Theranostics (2023)

Vein graft failure remains a significant clinical problem.Similar to other vascular diseases, stenosis of vein grafts is caused by several cell lines; however, the sources of these cells remain unclear.The objective of this study was to investigate the cellular sources that reshape vein grafts.By analyzing transcriptomics data and constructing inducible lineage-tracing mouse models, we investigated the cellular components of vein grafts and their fates.The sc-RNAseq data suggested that Sca-1+ cells were vital players in vein grafts and might serve as progenitors for multilineage commitment.By generating a vein graft model in which the venae cavae from C57BL/6J wild-type mice were transplanted adjacent to the carotid arteries of Sca-1(Ly6a)-CreERT2; Rosa26-tdTomato mice, we demonstrated that the recipient Sca-1+ cells dominated reendothelialization and the formation of adventitial microvessels, especially at the perianastomotic regions.In turn, using chimeric mouse models, we confirmed that the Sca-1+ cells that participated in reendothelialization and the formation of adventitial microvessels all had a non-bone-marrow origin, whereas bone-marrow-derived Sca-1+ cells differentiated into inflammatory cells in vein grafts.Furthermore, using a parabiosis mouse model, we confirmed that non-bone-marrow-derived circulatory Sca-1+ cells were vital for the formation of adventitial microvessels, whereas Sca-1+ cells derived from local carotid arteries were the source of endothelium restoration.Using another mouse model in which venae cavae from Sca-1 (Ly6a)-CreERT2; Rosa26-tdTomato mice were transplanted adjacent to the carotid arteries of C57BL/6J wild-type mice, we confirmed that the donor Sca-1+ cells were mainly responsible for smooth muscle cells commitment in the neointima, particularly at the middle bodies of vein grafts.In addition, we provided evidence that knockdown/knockout of Pdgfrα in Sca-1+ cells decreased the cell potential to generate SMCs in vitro and decreased number of intimal SMCs in vein grafts.Our findings provided cell atlases of vein grafts, which demonstrated that recipient carotid arteries, donor veins, non-bone-marrow circulation, and the bone marrow provided diverse Sca-1+ cells/progenitors that participated in the reshaping of vein grafts.
Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma
Authors: Peng Chen, Xiaoyao Cai, Ganen Mu, Yuansheng Duan, Chao Jing, Zhimou Yang, Cuihong Yang, Xudong Wang
Journal: Theranostics (2023)

Rationale: Although surgery, radioiodine therapy, and thyroid hormone therapy are the primary clinical treatments for differentiated thyroid carcinoma (DTC), effective therapy for locally advanced or progressive DTC remains challenging.BRAF V600E, the most common BRAF mutation subtype, is highly related to DTC.Previous studies prove that combination of kinase inhibitors and chemotherapeutic drugs may be a potential approach for DTC treatment.In this study, a supramolecular peptide nanofiber (SPNs) co-loaded with dabrafenib (Da) and doxorubicin (Dox) was constructed for targeted and synergistic therapy with BRAF V600E + DTC.Methods: A self-assembling peptide nanofiber (Biotin-G D F D F D YGRGD, termed SPNs) bearing biotin at the N-terminus and a cancer-targeting ligand RGD at the C-terminus was used as a carrier for co-loading Da and Dox.D-phenylalanine and D-tyrosine ( D F D F D Y) are used to improve the stability of peptides in vivo.Under multiple non-covalent interactions, SPNs/Da/Dox assembled into longer and denser nanofibers.RGD ligand endows self-assembled nanofibers with targeting cancer cells and co-delivery, thereby improving cellular uptake of payloads.Results: Both Da and Dox indicated decreased IC50 values upon encapsulation in SPNs.Co-delivery of Da and Dox by SPNs exhibited the strongest therapeutic effect in vitro and in vivo by inhibiting ERK phosphorylation in BRAF V600E mutant thyroid cancer cells.Moreover, SPNs enable efficient drug delivery and lower Dox dosage, thereby significantly reducing its side effects. Conclusion:This study proposes a promising paradigm for the synergistic treatment of DTC with Da and Dox using supramolecular self-assembled peptides as carriers.
Deletion of Calhm2 alleviates MPTP-induced Parkinson's disease pathology by inhibiting EFHD2-STAT3 signaling in microglia
Authors: Xuena Bo, Fei Xie, Jingdan Zhang, Runze Gu, Xiaoheng Li, Shuoshuo Li, Zengqiang Yuan, Jinbo Cheng
Journal: Theranostics (2023)

Background: Neuroinflammation is involved in the development of Parkinson's disease (PD).Calhm2 plays an important role in the development of microglial inflammation, but whether Calhm2 is involved in PD and its regulatory mechanisms are unclear.Methods: To study the role of Calhm2 in the development of PD, we utilized conventional Calhm2 knockout mice, microglial Calhm2 knockout mice and neuronal Calhm2 knockout mice, and established the MPTP-induced PD mice model.Moreover, a series of methods including behavioral test, immunohistochemistry, immunofluorescence, real-time polymerase chain reaction, western blot, mass spectrometry analysis and co-immunoprecipitation were utilized to study the regulatory mechanisms.Results: We found that both conventional Calhm2 knockout and microglial Calhm2 knockout significantly reduced dopaminergic neuronal loss, and decreased microglial numbers, thereby improving locomotor performance in PD model mice.Mechanistically, we found that Calhm2 interacted with EFhd2 and regulated downstream STAT3 signaling in microglia.Knockdown of Calhm2 or EFhd2 both inhibited downstream STAT3 signaling and inflammatory cytokine levels in microglia. Conclusion:We demonstrate the important role of Calhm2 in microglial activation and the pathology of PD, thus providing a potential therapeutic target for microglia-mediated neuroinflammation-related diseases.
Alarmin IL-33 orchestrates antitumoral T cell responses to enhance sensitivity to 5-fluorouracil in colorectal cancer
Authors: Mengjia Song, Jieying Yang, Muping Di, Ye Hong, Qiuzhong Pan, Yufei Du, Tong Xiang, Juan Liu, Yan Tang, Qijing Wang, Yongqiang Li, Jia He, Hao Chen, Jingjing Zhao, Desheng Weng, Yizhuo Zhang, Jian-Chuan Xia
Journal: Theranostics (2023)

Rationale: Resistance to 5-fluorouracil (5-FU) chemotherapy remains the main barrier to effective clinical outcomes for patients with colorectal cancer (CRC). A better understanding of the detailed mechanisms underlying 5-FU resistance is needed to increase survival. Interleukin (IL)-33 is a newly discovered alarmin-like molecule that exerts pro- and anti-tumorigenic effects in various cancers. However, the precise role of IL-33 in CRC progression, as well as in the development of 5-FU resistance, remains unclear. Methods: High-quality RNA-sequencing analyses were performed on matched samples from patients with 5-FU-sensitive and 5-FU-resistant CRC. The clinical and biological significance of IL-33, including its effects on both T cells and tumor cells, as well as its relationship with 5-FU chemotherapeutic activity were examined in ex vivo, in vitro and in vivo models of CRC. The molecular mechanisms underlying these processes were explored. Results: IL-33 expressed by tumor cells was a dominant mediator of antitumoral immunity in 5-FU-sensitive patients with CRC. By binding to its ST2 receptor, IL-33 triggered CD4+ (Th1 and Th2) and CD8+ T cell responses by activating annexin A1 downstream signaling cascades. Mechanistically, IL-33 enhanced the sensitivity of CRC cells to 5-FU only in the presence of T cells, which led to the activation of both tumor cell-intrinsic apoptotic and immune killing-related signals, thereby synergizing with 5-FU to induce apoptosis of CRC cells. Moreover, injured CRC cells released more IL-33 and the T cell chemokines CXCL10 and CXCL13, forming a positive feedback loop to further augment T cell responses. Conclusions: Our results identified a previously unrecognized connection between IL-33 and enhanced sensitivity to 5-FU. IL-33 created an immune-active tumor microenvironment by orchestrating antitumoral T cell responses. Thus, IL-33 is a potential predictive biomarker for 5-FU chemosensitivity and favorable prognosis and has potential as a promising adjuvant immunotherapy to improve the clinical benefits of 5-FU-based therapies in the treatment of CRC.
Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer
Authors: Yi Wang, Yuqiu Li, Junpei Zhong, Miao Li, Youjia Zhou, Qing Lin, Siwen Zong, Wenting Luo, Jiayang Wang, Keqin Wang, Jie Wang, Lixia Xiong
Journal: Theranostics (2023)

Rationale: Breast cancer (BC), as one of the most frequently diagnosed cancer, has a poor prognosis due to the development of distant metastasis. Among the BC metastatic sites, lung is one of the most common sites. Caveolin-1 (Cav-1) is a functional membrane protein that plays a vital role in tumor metastasis. Although studies have revealed that Cav-1 levels were elevated in patients with advanced cancer, whether Cav-1 affects BC lung metastasis by influencing the formation of pre-metastatic niche (PMN) through exosomes has not been explored. Methods: Differential ultracentrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to verify the presence of exosomes. Transwell assays were used to examine the biological effects of exosomes containing Cav-1. Both in vitro cell cultures and mammary tumor cell-induced mouse models were used to assess the lung metastasis. The regulatory mechanisms of PMN formation were revealed using western blot, flow cytometry, RT-qPCR, immunofluorescence assays, gene overexpression assays and RNA interference assays. Results: Exosomes have critical functions in transporting Cav-1 between primary BC and metastatic organ microenvironments. Cav-1 in BC-derived exosomes can act as a signaling molecule to mediate intercellular communication and regulate the PMN before lung metastasis by regulating the expression of PMN marker genes and inflammatory chemokines in lung epithelial cells, promoting the secretion of tenascin-C (TnC) in lung fibroblasts to cause extracellular matrix (ECM) deposition, and inhibiting the PTEN/CCL2/VEGF-A signaling pathway in lung macrophages to facilitate their M2-type polarization and angiogenesis. Conclusion: Our study investigated the mechanisms of lung PMN formation induced by Cav-1 in BC-derived exosomes. Our data may provide new directions for exploring the mechanisms and developing treatment strategies of BC lung metastasis.
Recent advances in fluorescent probes of peroxynitrite: Structural, strategies and biological applications
Authors: Jiarao Sun, Xiaoli Cao, Wenjuan Lu, Yongchun Wei, Lingxiu Kong, Wei Chen, Xintian Shao, Yanfeng Wang
Journal: Theranostics (2023)

Peroxynitrite (ONOO-), owing to its high oxidative and nitrating stress, is associated with several physiological processes in addition to various pathological processes, including those related to neurodegenerative diseases and cancer. Detection of ONOO- at the cellular level is of great significance to understand its pathogenesis. To this end, a variety of fluorescent probes based on small molecules and nanoparticles (NPs) have been engineered and applied as excellent tools for imaging of ONOO- in cells as well as in their diverse biological applications. In this review, we highlight representative cases of fluorescent probes based on recognition mechanism and emphasize their response type (ratiometric, two-photon, long-wavelength/near-infrared, and targeting) in ONOO- detection in the last five years. We further discuss their design strategy, sensing mechanism, and application in bio-imaging and describe NP-based probes according to diverse nanoplatforms.
Ultrasound-controlled MXene-based Schottky heterojunction improves anti-infection and osteogenesis properties
Authors: Hongchuan Wang, Na Mu, Yaqi He, Xiaoguang Zhang, Jie Lei, Cao Yang, Liang Ma, Yong Gao
Journal: Theranostics (2023)

Background:The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic treatment and large bone defects.Sonodynamic therapy (SDT) is a new strategy that is widely used to overcome the problem of bacterial resistance to antibiotic therapy as well as poor tissue penetration using near-infrared light in photodynamic therapy (PDT).Therefore, it is necessary to develop a new sonosensitizer that can kill bacteria and promote bone repair.Methods: Herein, we developed a sonosensitizer, porphyrin metal-organic framework (HNTM), with a Schottky junction modified by Ti3C2 nanosheets (HN-Ti3C2) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration.Results: Ti3C2 greatly improves the acoustic catalytic performance by rapidly transferring the charge carriers generated by HNTM under ultrasound (US) irradiation, which killing drug-resistant bacteria through the generation of large amounts of reactive oxygen species (ROS).And HN-Ti3C2 shows excellent 99.75% antibacterial effectiveness against MRSA.In addition, HN-Ti3C2 generates a sonocurrent under low-intensity US to promote the repair of bone defects for a long time period.Mechanistic research using CCK-8 and RNA-seq showed that HN-Ti3C2 nanocomposites can promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis.In addition, after low-intensity US irradiation, HN-Ti3C2 promotes osteogenic differentiation via some key signaling pathways, including the calcium, Wnt, and TGF-beta signaling pathways, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG).In a MRSA-infected rat tibial osteomyelitis model, HN-Ti3C2 successfully eliminated the infection and significantly improved bone regeneration under US irradiation. Conclusion:This study indicates that engineered HN-Ti3C2 is a distinctive nanocomposite for successful osteomyelitis treatment.
Transformable prodrug nanoplatform <i>via</i> tumor microenvironment modulation and immune checkpoint blockade potentiates immunogenic cell death mediated cancer immunotherapy
Authors: Weijing Yang, Jinmeng Yi, Rongrong Zhu, Yichen Guo, Kaixin Zhang, Yongjian Cao, Xinyan Li, Jinjie Zhang, Zhenzhong Zhang, Yongjuan Li, Xiaoyuan Chen
Journal: Theranostics (2023)

Chemoimmunotherapy is a promising approach in cancer immunotherapy. However, its therapeutic efficacy is restricted by high reactive oxygen species (ROS) levels, an abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) as well as immune checkpoints for escaping immunosurveillance.
Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions
Authors: Haiyan Gao, Zhiping Cao, Huanhuan Liu, Lijuan Chen, Yan Bai, Qingxia Wu, Xuan Yu, Wei Wei, Meiyun Wang
Journal: Theranostics (2023)

Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.
Recent advances in GelMA hydrogel transplantation for musculoskeletal disorders and related disease treatment
Authors: Bin Lv, Li Lu, Liangcong Hu, Peng Cheng, Yiqiang Hu, Xudong Xie, Guandong Dai, Bobin Mi, Xin Liu, Guohui Liu
Journal: Theranostics (2023)

Increasing data reveals that gelatin that has been methacrylated is involved in a variety of physiologic processes that are important for therapeutic interventions. Gelatin methacryloyl (GelMA) hydrogel is a highly attractive hydrogels-based bioink because of its good biocompatibility, low cost, and photo-cross-linking structure that is useful for cell survivability and cell monitoring. Methacrylated gelatin (GelMA) has established itself as a typical hydrogel composition with extensive biomedical applications. Recent advances in GelMA have focused on integrating them with bioactive and functional nanomaterials, with the goal of improving GelMA's physical, chemical, and biological properties. GelMA's ability to modify characteristics due to the synthesis technique also makes it a good choice for soft and hard tissues. GelMA has been established to become an independent or supplementary technology for musculoskeletal problems. Here, we systematically review mechanism-of-action, therapeutic uses, and challenges and future direction of GelMA in musculoskeletal disorders. We give an overview of GelMA nanocomposite for different applications in musculoskeletal disorders, such as osteoarthritis, intervertebral disc degeneration, bone regeneration, tendon disorders and so on.
Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment
Authors: Chenyang Yin, ZeKun Wang, Chunxue Dai, Bangjia Yang, Weiyun Wang, Endong Yang, Feng Guo, Cundong Fan, Pu Zhang, Jikui Sun, Dongdong Sun
Journal: Theranostics (2023)

Background: Singlet oxygen ( 1 O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features.However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1 O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive.Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/ photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources.Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results:The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne.After i.v.injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne.With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1 O2 via a loaded photosensitizer.PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further.Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.
The role of lipid metabolic reprogramming in tumor microenvironment
Authors: Kai Yang, Xiaokun Wang, Chenghu Song, Zhao He, Ruixin Wang, Yongrui Xu, Guanyu Jiang, Yuan Wan, Jie Mei, Wenjun Mao
Journal: Theranostics (2023)

Metabolic reprogramming is one of the most important hallmarks of malignant tumors.Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME).In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers.Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy.Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism.Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.
Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1
Authors: Yinghua Li, Danyang Chen, Jingyao Su, Mingkai Chen, Tianfeng Chen, Wei Jia, Bing Zhu
Journal: Theranostics (2023)

Background: Influenza A (H1N1) virus is an acute respiratory infectious disease that causes massive morbidity and mortality worldwide. As an essential trace element, selenium is widely applied in the treatment of various diseases because of its functions of enhancing immune response, antioxidant and antiviral mutation. In this study, we constructed the selenium-containing metal complex drug delivery system Ru(biim)(PhenSe)2 (RuSe), and investigated the anti-influenza virus efficacy and the potential antiviral mechanism for RuSe. Methods: The inhibitory effect of RuSe on influenza-mediated apoptosis was examined by cell count assay, cell cycle assay, Annenxin-V assay, TUNEL-DAPI assay and reactive oxygen species level determination. Virulence assay, PCR and neuraminidase inhibition assay revealed the inhibition of RuSe on influenza virus. At the level of animal experiments, two animal models were used to clarify the role of RuSe through HE staining, immunohistochemical staining, cytokine determination, selenium metabolism determination and selenium protein expression level determination. Results: The results of this study confirm that RuSe enhances the expression levels of selenium proteins GPx1 and TrxR1 by regulating selenium metabolism, thereby inhibiting viral replication and assembly and regulating virus-mediated mitochondria-related apoptosis. On the other hand, animal experiments show that RuSe can reduce lung tissue inflammation and inhibit lung tissue cell apoptosis in mice, and improve the survival state of mice. In addition, RuSe significantly improves the low immune response of Se-deficient mice by regulating selenium metabolism, and effectively alleviated lung fibrosis and lung tissue apoptosis in Se-deficient mice. Conclusions: This study suggests that RuSe provides a promising new approach for the clinical treatment of influenza virus.